Abstract
Stimulus substitution models posit that placebo responses are due to pairings of conditional and unconditional stimuli. Expectancy theory maintains that conditioning trials produce placebo response expectancies, rather than placebo responses, and that the expectancies elicit the responses. We tested these opposing models by providing some participants with information intended to impede the formation of placebo expectancies during conditioning trials and by assessing placebo expectancies. Although conditioning trials significantly enhanced placebo responding, this effect was eliminated by adding expectancies to the regression equation, indicating that the effect of pairing trials on placebo response was mediated completely by expectancy. Verbal information reversed the effect of conditioning trials on both placebo expectancies and placebo responses, and the magnitude of the placebo effect increased significantly over 10 extinction trials. These data disconfirm a stimulus substitution explanation and provide strong support for an expectancy interpretation of the conditioned placebo enhancement produced by these methods.

Placebo and Nocebo in Cardiovascular Health: Implications for Healthcare, Research, and the Doctor-Patient RelationshipJournal of the American College of Cardiology, Volume 49, Issue 4, 30 January 2007, Pages 415-421
Brian Olshansky

Abstract
Despite treatments proven effective by sound study designs and robust end points, placebos remain integral to elicit effective medical care. The authenticity of the placebo response has been questioned, but placebos likely affect pain, functionality, symptoms, and quality of life. In cardiology, placebos influence disability, syncope, heart failure, atrial fibrillation, angina, and survival. Placebos vary in strength and efficacy. Compliance to placebo affects outcomes. Nocebo responses can explain some adverse clinical outcomes. A doctor may be an unwitting contributor to placebo and nocebo responses. Placebo and nocebo mechanisms, not well understood, are likely multifaceted. Placebo and nocebo use is common in practice. A successful doctor-patient relationship can foster a strong placebo response while mitigating any nocebo response. The beneficial effects of placebo, generally undervalued, hard to identify, often unrecognized, but frequently used, help define our profession. The role of the doctor in healing, above the therapy delivered, is immeasurable but powerful. An effective placebo response will lead to happy and healthy patients. Imagine instead the future of healthcare relegated to a series of guidelines, tests, algorithms, procedures, and drugs without the human touch. Healthcare, rendered by a faceless, uncaring army of protocol aficionados, will miss an opportunity to deliver an effective placebo response. Wise placebo use can benefit patients and strengthen the medical profession.